Early-life microbial intervention reduces colitis risk promoted by antibiotic-induced gut dysbiosis
Early-life microbial intervention reduces colitis risk promoted by antibiotic-induced gut dysbiosis
Summary Perturbations in the early life gut microbiome are associated with increased risk to complex immune disorder like inflammatory bowel diseases. We previously showed maternal antibiotic-induced gut dysbiosis vertically passed to offspring increases experimental colitis risk in IL-10 gene deficient (IL-10?/?) mice. While this could arise from emergence of pathobionts or loss/lack of essential microbes needed for appropriate immunological education, our findings suggest the latter. A dominant Bacteroides strain absent following antibiotic-induced perturbation was cultivated from murine fecal samples. Addition of this strain into mice with antibiotic-induced dysbiosis significantly promoted immune tolerance and reduced incidence of colitis in IL-10?/? mice, but only if engrafted early in life, and not during adulthood. Thus, key members of the gut microbiome are essential for development of immune tolerance to commensal microbes in early life and their addition in presence of gut dysbiosis during this period can reduce colitis risk in genetically prone hosts. HighlightsSpecific gut microbes promote early life immune tolerance to key commensal microbesLoss of early life keystone microbes increases colitis risk in genetically prone hostsEmergence of absent commensal microbes late in life worsened colitis outcomeEarly life exposure to a missing keystone Bacteroides strain reduced colitis risk
Sakatani Aki、Lee Sonny T.M.、Yang Karen、Shan Yue、Antonopoulos Dionysios A.、Leone Vanessa、Crosson Sean、Kiefl Evan、Delmont Tom O.、Eren A. Murat、Cham Candace、Sogin Mitchell、Miyoshi Jun、Yousef Mahmoud、Chang Eugene B.、Miyoshi Sawako
Department of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery||Division of Biology, Kansas State UniversityDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryBiosciences Division, Argonne National Laboratory, 9700 S. Cass Avenue LemontDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryDepartment of Microbiology and Molecular Genetics, Michigan State University, 5161 Biomedical Physical SciencesDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery||Graduate Program in Biophysical Sciences, The University of Chicago, Gordon Center for Integrative ScienceDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery||G¨|nomique M¨|tabolique, Genoscope, Institut Fran?ois Jacob, CEA, CNRS, Univ Evry, Universit¨| Paris-Saclay, EvryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryJosephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological LaboratoryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery||Department of Gastroenterology and Hepatology, Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka-shiUndergraduate Program, Department of Computer Science, The University of Chicago John Crerar LibraryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical DiscoveryDepartment of Medicine, Knapp Center for Biomedical Discovery, The University of Chicago Knapp Center for Biomedical Discovery||Department of General Medicine, Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka-shi
微生物学基础医学
Inflammatory bowel diseasesgut microbiotamicrobial perturbationshost-microbiota interactionsimmunological developmentimmune toleranceBacteroides
Sakatani Aki,Lee Sonny T.M.,Yang Karen,Shan Yue,Antonopoulos Dionysios A.,Leone Vanessa,Crosson Sean,Kiefl Evan,Delmont Tom O.,Eren A. Murat,Cham Candace,Sogin Mitchell,Miyoshi Jun,Yousef Mahmoud,Chang Eugene B.,Miyoshi Sawako.Early-life microbial intervention reduces colitis risk promoted by antibiotic-induced gut dysbiosis[EB/OL].(2025-03-28)[2025-06-27].https://www.biorxiv.org/content/10.1101/2020.03.11.987412.点此复制
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